Table 1 5 The Principal Lipoproteins.

Composition (%) Lipoprotei Size n (nm) Protei Free Cholester Triglyceri Phospholip Origin n Cholester ol Esters de id yl 2 ... 4 3 ... 16 90 ... 55 3 ... 17 Intestine Capillari es Liver and intestine VLDL

Chylomicro 75 10 2 ns 00 Chylomicro 30 80 . . . n remnants Very low 30 80 8 density lipoproteins (VLDL) Intermediat 25 40 10 e-density lipoproteins (IDL) Low20 density lipoproteins (LDL) 20

25

40

20

46

21

IDL

High7.5 10 50 density lipoproteins (HDL)

16

25

Liver and intestine

Table 3 3 Human Immunoglobulins.a

Immunoglobulin Function

Heavy Additional Structure Chain Chain

g1,

Plasma Concentration (mg/dL) 1000

IgG

Complement activation Localized protection in external secretions (tears, intestinal

g2,

Monomer

g3, g4
alpha 1, alpha2

IgA

J, SC

Monomer; 200 dimer with J or SC chain; trimer with J chain

secretions, etc) IgM IgD Complement activation Antigen recognition by B cells u dlta J Pentamer 120 with J chain Monomer 3

IgE

Reagin activity; e releases histamine from basophils and mast cells

Monomer

0.05

Table 3 2 Examples of Cytokines and Their Clinical Relevance.

Cytokine Interleukin-1

Cellular Sources Macrophages

Major Activities Activation of T cells and macrophages; promotion of inflammation

Clinical Relevance Implicated in the pathogenesis of septic shock, rheumatoid arthritis, and atherosclerosis Used to induce lymphokine-activated killer cells; used in the treatment of metastatic renal-cell carcinoma, melanoma, and various other tumors

Interleukin-2

Type 1 (TH1) helper T cells

Activation of lymphocytes, natural killer cells, and macrophages

Interleukin-4

Type 2 (TH2) helper T cells, mast cells, basophils, and eosinophils

Activation of As a result of its ability to lymphocytes, monocytes, stimulate IgE production, and IgE class switching plays a part in mast-cell sensitization and thus in allergy and in defense against nematode infections Differentiation of eosinophils Monoclonal antibody against interleukin-5 used

Interleukin-5

Type 2 (TH2) helper T cells,

mast cells, and eosinophils

to inhibit the antigeninduced late-phase eosinophilia in animal models of allergy Activation of lymphocytes; differentiation of B cells; stimulation of the production of acute-phase proteins Chemotaxis of neutrophils, basophils, and T cells Overproduced in Castleman's disease; acts as an autocrine growth factor in myeloma and in mesangial proliferative glomerulonephritis Levels are increased in diseases accompanied by neutrophilia, making it a potentially useful marker of disease activity

Interleukin-6

Type 2 (TH2) helper T cells and macrophages

Interleukin-8

T cells and macrophages

Interleukin-11 Bone marrow stromal cells

Stimulation of the Used to reduce production of acute-phase chemotherapy-induced proteins thrombocytopenia in patients with cancer Stimulation of the May be useful as an production of adjuvant for vaccines interferon gyma by type 1 (TH1) helper T cells and by natural killer cells; induction of type 1 (TH1) helper T cells Treatment with antibodies against tumor necrosis factor -alpha beneficial in rheumatoid arthritis Implicated in the pathogenesis of multiple sclerosis and insulindependent diabetes mellitus May be useful therapeutic agent in multiple sclerosis and myasthenia gravis Used to reduce neutropenia after chemotherapy for tumors

Interleukin-12 Macrophages and B cells

Tumor necrosis Macrophages, Promotion of factor alpha natural killer inflammation cells, T cells, B cells, and mast cells Lymphotoxin Type 1 (TH1) (tumor necrosis helper T cells factor beta) and B cells Promotion of inflammation

Transforming growth factor beta Granulocytemacrophage colony-

T cells, Immunosuppression macrophages, B cells, and mast cells T cells, macrophages, natural killer Promotion of the growth of granulocytes and monocytes

stimulating factor

cells, and B cells

and in ganciclovir-treated patients with AIDS; used to stimulate cell production after bone marrow transplantation

Interferonalpha

Virally infected Induction of resistance of Used to treat AIDScells cells to viral infection related Kaposi sarcoma, melanoma, chronic hepatitis B infection, and chronic hepatitis C infection

Interferon-beta Virally infected Induction of resistance of Used to reduce the cells cells to viral infection frequency and severity of relapses in multiple sclerosis Interferongyma Type 1 (TH1) helper T cells and natural killer cells Activation of macrophages; inhibition of type 2 (TH2) helper T cells Used to enhance the killing of phagocytosed bacteria in chronic granulomatous disease

Table 4 1 Nerve Fiber Types in Mammalian Nerve.a

Fiber Type Function

Fiber Diameter (um) 12 20 5 12 3 6 2 5

Conduction Velocity (m/s) 70 120 30 70 15 30 12 30

Spike Duration (ms)

Absolute Refractory Period (ms)

A alpha beta gyma delta Proprioception; somatic motor Touch, pressure Motor to muscle spindles Pain, cold, touch

0.4 0.5

0.4 1

B C

Preganglionic autonomic

<3

3 15

1.2

1.2

Dorsal root Pain, temperature, 0.4 1.2 some mechanoreception Sympathetic Postganglionic sympathetic 0.3 1.3

0.5 2

0.7 2.3

Table 4 2 Numerical Classification Sometimes Used for Sensory Neurons.

Number Origin Ia Ib II III IV Muscle spindle, annulo-spiral ending Golgi tendon organ Pain and cold receptors; some touch receptors Pain, temperature, and other receptors

Fiber Type A -alpha A -alpha A -delta Dorsal root C

Muscle spindle, flower-spray ending; touch, pressure A -beta

Table 4 3 Relative Susceptibility of Mammalian A, B, and C Nerve Fibers to Conduction Block Produced by Various Agents.

Susceptibility to: Hypoxia Pressure Local anesthetics

Most Susceptible B A C

Intermediate A B B

Least Susceptible C C A

Table 7 1 Examples of Colocalization of Small-Molecule Transmitters with Neuropeptides.

Small-Molecule Transmitter Monoamines Acetylcholine

Neuropeptide

Enkephalin, calcitonin-gene-related peptide, galanin, gonadotropin-releasing hormone, neurotensin, somatostatin, substance P, vasoactive intestinal polypeptide Cholecystokinin, enkephalin, neuropeptide Y, substance P, vasoactive intestinal polypeptide Cholecystokinin, enkephalin, neurotensin Enkephalin, neuropeptide Y, neurotensin, somatostatin, vasopressin Enkephalin, neuropeptide Y, neurotensin, substance P Substance P Neurotensin Cholecystokinin, enkephalin, somatostatin, substance P, thyrotropin-releasing hormone

Serotonin Catecholamines Dopamine Norepinephrine Epinephrine Amino Acids Glutamate Glycine GABA

Table 18 4 Temperature-Regulating Mechanisms.

Mechanisms activated by cold Shivering Hunger Increased voluntary activity Increased secretion of norepinephrine and epinephrine Decreased heat loss Cutaneous vasoconstriction Curling up Horripilation Mechanisms activated by heat Increased heat loss Cutaneous vasodilation Sweating

Increased respiration Decreased heat production Anorexia Apathy and inertia

Table 19 1 Aphasias. Characteristic Responses of Patients with Lesions in Various Areas When Shown a Picture of a Chair.

Type of Aphasia and Site of Lesion Nonfluent (Broca s area) Fluent (Wernicke s area) Fluent (areas 40, 41, and 42; conduction aphasia) Anomic (angular gyrus)

Characteristic Naming Errors "Tssair" "Stool" or "choss" (neologism) "Flair . . . no, swair . . . tair." "I know what it is . . . I have a lot of them."

Table 20 2 Effect of Variations in the Concentrations of Thyroid Hormone-Binding Proteins in the Plasma on Various Parameters of Thyroid Function after Equilibrium Has Been Reached.

Condition

Concentrations of Binding Proteins

Total Plasma T4, T3, RT3 High Low High

Free Plasma T4, T3, RT3 High Low Normal

Plasma Clinical TSH State

Hyperthyroidism Hypothyroidism Estrogens, methadone, heroin, major tranquilizers, clofibrate Glucocorticoids,

Normal Normal High

Low High

Hyperthyroid Hypothyroid

Normal Euthyroid

Low

Low

Normal

Normal Euthyroid

androgens, danazol, asparaginase

Table 20 3 Causes of Congenital Hypothyroidism.

Maternal iodine deficiency Fetal thyroid dysgenesis Inborn errors of thyroid hormone synthesis Maternal antithyroid antibodies that cross the placenta Fetal hypopituitary hypothyroidism

Table 20 4 Causes of Hyperthyroidism.

Thyroid overactivity Solitary toxic adenoma Toxic multinodular goiter Hashimoto thyroiditis TSH-secreting pituitary tumor Mutations causing constitutive activation of TSH receptor Other rare causes Extrathyroidal Administration of T3 or T4 (factitious or iatrogenic hyperthyroidism) Ectopic thyroid tissue

Table 20 5 Physiologic Effects of Thyroid Hormones.

Target Tissue Heart

Effect Chronotropic Inotropic

Mechanism Increased number of -beta-adrenergic receptors Enhanced responses to circulating catecholamines Increased proportion of -alpha-myosin heavy chain (with higher ATPase activity)

Adipose tissue Muscle Bone Nervous system Gut Lipoprotein Other

Catabolic Catabolic Developmental Developmental Metabolic Metabolic Calorigenic

Stimulated lipolysis Increased protein breakdown Promote normal growth and skeletal development Promote normal brain development Increased rate of carbohydrate absorption Formation of LDL receptors Stimulated oxygen consumption by metabolically active tissues (exceptions: testes, uterus, lymph nodes, spleen, anterior pituitary) Increased metabolic rate

Table 21 2 Substances with Insulin-Like Activity in Human Plasma.

Insulin Proinsulin Nonsuppressible insulin-like activity (NSILA) Low-molecular-weight fraction IGF-I IGF-II High-molecular-weight fraction (mostly IGF bound to protein)

Table 21 3 Principal Actions of Insulin.

Rapid (seconds) Increased transport of glucose, amino acids, and K+ into insulin-sensitive cells Intermediate (minutes) Stimulation of protein synthesis Inhibition of protein degradation Activation of glycolytic enzymes and glycogen synthase Inhibition of phosphorylase and gluconeogenic enzymes Delayed (hours) Increase in mRNAs for lipogenic and other enzymes

Table 21 4 Effects of Insulin on Various Tissues.

Adipose tissue Increased glucose entry Increased fatty acid synthesis Increased glycerol phosphate synthesis Increased triglyceride deposition Activation of lipoprotein lipase Inhibition of hormone-sensitive lipase Increased K+ uptake Muscle Increased glucose entry Increased glycogen synthesis Increased amino acid uptake Increased protein synthesis in ribosomes Decreased protein catabolism

Decreased release of gluconeogenic amino acids Increased ketone uptake Increased K+ uptake Liver Decreased ketogenesis Increased protein synthesis Increased lipid synthesis Decreased glucose output due to decreased gluconeogenesis, increased glycogen synthesis, and increased glycolysis General Increased cell growth

Table 21 5 Glucose Transporters in Mammals.

Function

Km (mM)a

Major Sites of Expression

Secondary active transport (Na1glucose cotransport) SGLT 1 SGLT 2 Facilitated diffusion GLUT 1 Basal glucose uptake 1 2 Placenta, blood-brain barrier, brain, red cells, kidneys, colon, many other organs B cells of islets, liver, epithelial cells of small intestine, kidneys Brain, placenta, kidneys, Absorption of glucose Absorption of glucose 0.1 1.0 Small intestine, renal tubules 1.6 Renal tubules

GLUT 2

B-cell glucose sensor; 12 20 transport out of intestinal and renal epithelial cells Basal glucose uptake <1

GLUT 3

many other organs GLUT 4 Insulin-stimulated glucose uptake Fructose transport None 5 Skeletal and cardiac muscle, adipose tissue, other tissues Jejunum, sperm Pseudogene Liver, ? other tissues

GLUT 5 GLUT 6 GLUT 7

1 2

Glucose 6-phosphate ransporter in endoplasmic reticulum

Table 21 6 Factors Affecting Insulin Secretion.

Stimulators Glucose Mannose Amino acids (leucine, arginine, others) Intestinal hormones (GIP, GLP-1 [7 36], gastrin, secretin, CCK; others?) beta-Keto acids Acetylcholine Glucagon Cyclic AMP and various cAMP-generating substances beta-Adrenergic stimulators Theophylline Sulfonylureas

Inhibitors Somatostatin 2-Deoxyglucose Mannoheptulose alpha-Adrenergic stimulators (norepinephrine, epinephrine) beta-Adrenergic blockers (propranolol) Galanin Diazoxide Thiazide diuretics K+ depletion Phenytoin Alloxan Microtubule inhibitors Insulin

Table 21 8 Factors Affecting Glucagon Secretion.

Stimulators Amino acids (particularly the glucogenic amino acids: alanine, serine, glycine, cysteine, and threonine) CCK, gastrin Cortisol Exercise Infections Other stresses beta-Adrenergic stimulators Theophylline Acetylcholine

Inhibitors Glucose Somatostatin Secretin FFA Ketones Insulin Phenytoin alpha-Adrenergic stimulators GABA

Table 22 4 Typical Effects of Cortisol on the White and Red Blood Cell Counts in Humans (Cells/ L).

Cell White blood cells Total PMNs Lymphocytes Eosinophils Basophils Monocytes Red blood cells

Normal 9000 5760 2370 270 60 450 5 million

Cortisol-Treated 10,000 8330 1080 20 30 540 5.2 million

Table 22 5 Typical Plasma Electrolyte Levels in Normal Humans and Patients with Adrenocortical Diseases.

Plasma Electolytes (mEq/L)

State Normal Adrenal insufficiency Primary hyperaldosteronism

Na+ 142 120 145

K+ 4.5 6.7 2.4

Cl 105 85 96

HCO3 25 25 41

Table 22 6 Conditions that Increase Aldosterone Secretion.

Glucocorticoid secretion also increased Surgery Anxiety Physical trauma Hemorrhage Glucocorticoid secretion unaffected High potassium intake Low sodium intake Constriction of inferior vena cava in thorax Standing Secondary hyperaldosteronism (in some cases of congestive heart failure, cirrhosis, and nephrosis)

Table 22 7 Second Messengers Involved in the Regulation of Aldosterone Secretion.

Secretagogue ACTH Angiotensin II K

+

Intracellular Mediator Cyclic AMP, protein kinase A Diacylglycerol, protein kinase C Ca2+ via voltage-gated Ca2+ channels

Table 24 3 Stimuli that Affect Growth Hormone Secretion in Humans.

Stimuli that increase secretion Hypoglycemia 2-Deoxyglucose Exercise Fasting Increase in circulating levels of certain amino acids Protein meal Infusion of arginine and some other amino acids Glucagon Stressful stimuli Pyrogen Lysine vasopressin Various psychologic stresses Going to sleep
L-Dopa and

alpha-adrenergic agonists that penetrate the brain

Apomorphine and other dopamine receptor agonists Estrogens and androgens Stimuli that decrease secretion REM sleep Glucose Cortisol FFA Medroxyprogesterone Growth hormone and IGF-I

Table 25 3 Factors Affecting the Secretion of Human Prolactin and Growth Hormone.

Factor Sleep Nursing Breast stimulation in nonlactating women Stress Hypoglycemia Strenuous exercise Sexual intercourse in women Pregnancy Estrogens Hypothyroidism TRH Phenothiazines, butyrophenones Opioids Glucose Somatostatin
L-Dopa

Prolactina I+ I++ I I+ I I I I++ I I I+ I+ I N N D+ D+ D+

Growth Hormonea I+ N N I+ I+ I N N I N N N I D D+ I+ I+ I

Apomorphine Bromocriptine and related ergot derivatives

I, moderate increase; I+, marked increase; I++, very marked increase; N, no change; D, moderate decrease; D+, marked decrease; TRH, thyrotropin-releasing hormone.

Table 25 7 Twenty-Four-Hour Production Rates of Sex Steroids in Women at Different Stages of the Menstrual Cycle.

Sex Steroids Progesterone (mg) 17-hydroxyprogesterone (mg) Dehydroepiandrosterone (mg) Androstenedione (mg) Testosterone (ug) Estrone (ug) Estradiol (ug)

Early Follicular 1.0 0.5 7.0 2.6 144.0 50.0 36.0

Preovulatory 4.0 4.0 7.0 4.7 171.0 350.0 380.0

Midluteal 25.0 4.0 7.0 3.4 126.0 250.0 250.0

Table 25 9 Hormone Levels in Human Maternal Blood during Normal Pregnancy.

Hormone hCG Relaxin hCS Estradiol Estriol Progesterone Prolactin

Approximate Peak Value 5 mg/mL 1 ng/mL 15 mg/mL 16 ng/mL 14 ng/mL 190 ng/mL 200 ng/mL

Time of Peak Secretion First trimester First trimester Term Term Term Term Term

Table 25 10 Composition of Colostrum and Milk.*

Component Water, g Lactose, g

Human Colostrum ... 5.3

Human Milk 88 6.8

Cows' Milk 88 5.0

Protein, g Casein: lactalbumin ratio Fat, g Linoleic acid Sodium, mg Potassium, mg Chloride, mg Calcium, mg Magnesium, mg Phosphorus, mg Iron, mg Vitamin A, ug Vitamin D, ug Thiamine, ug Riboflavin, ug Nicotinic acid, ug Ascorbic acid, mg

2.7 ... 2.9 ... 92 55 117 31 4 14 0.09 89 ... 15 30 75 4.4

a 2

1.2 1:2 3.8 8.3% of fat 15 55 43 33 4 15 0.15 53 0.03 16 43 172 4.3

a a a

3.3 3:1 3.7 1.6% of fat 58 138 103 125 12 100 0.10a 34 0.06a 42 157 85 1.6a

Table 26 1 Contents of Normal Gastric Juice (Fasting State).

Cations: Na+, K+, Mg2+, H+ (pH approximately 1.0) Anions: Cl , HPO42 , SO42 Pepsins Lipase Mucus Intrinsic factor

Table 26 2 Principal Digestive Enzymes.*

Source

Enzyme

Activator

Substrate

Catalytic Function or Products Hydrolyzes 1:4alpha linkages, producing -alphalimit dextrins, maltotriose, and maltose Fatty acids plus 1,2-diacylglycerols Cleave peptide bonds adjacent to aromatic amino acids Fatty acids and glycerol Cleave peptide bonds on carboxyl side of basic amino acids (arginine or lysine) Cleave peptide bonds on carboxyl side of aromatic amino acids

Salivary glands

Salivary alphaamylase

Cl

Starch

Lingual glands Stomach

Lingual lipase Pepsins (pepsinogens) HCl

Triglycerides Proteins and polypeptides

Gastric lipase Exocrine pancreas

Triglycerides

Trypsin (trypsinogen) Enteropeptidase Proteins and polypeptides

Chymotrypsins Trypsin (chymotrypsinogens)

Proteins and polypeptides

Elastase (proelastase) Trypsin

Elastin, some Cleaves bonds on other proteins carboxyl side of aliphatic amino acids Proteins and polypeptides Cleave carboxyl terminal amino acids that have aromatic or branched aliphatic side chains Cleave carboxyl terminal amino

Carboxypeptidase A Trypsin (procarboxypeptidase A)

Carboxypeptidase B Trypsin (procarboxypeptidase

Proteins and polypeptides

B) Colipase (procolipase) Trypsin Fat droplets

acids that have basic side chains Facilitates exposure of active site of pancreaticlipase Monoglycerides and fatty acids Cholesterol Cholesterol Same as salivary alpha-amylase Nucleotides Nucleotides

Pancreatic lipase Bile salt-acid lipase Cholesteryl ester hydrolase Pancreatic alphaamylase Ribonuclease Deoxyribonuclease Phospholipase A2 (pro-phospholipase A2) Intestinal mucosa Enteropeptidase Aminopeptidases

...

Triglycerides Cholesteryl esters

... Cl ... ... Trypsin

Cholesteryl esters Starch RNA DNA

Phospholipids Fatty acids, lysophospholipids

... ...

Trypsinogen Polypeptides

Trypsin Cleave amino terminal amino acid from peptide Cleave carboxyl terminal amino acid from peptide Cleave between residues in midportion of peptide Two amino acids

Carboxypeptidases

...

Polypeptides

Endopeptidases

...

Polypeptides

Dipeptidases Maltase

... ...

Dipeptides

Maltose, Glucose maltotriose, alpha-dextrins Lactose Sucrose; also maltotriose Galactose and glucose Fructose and glucose

Lactase Sucrasea

... ...

and maltose alpha-Dextrinase

a

...

alphaDextrins, maltose maltotriose Trehalose

Glucose

Trehalase Nuclease and related enzymes Cytoplasm Various peptidases of mucosal cells

... ...

Glucose

Nucleic acids Pentoses and purine and pyrimidine bases Di-, tri-, and tetrapeptides Amino acids

...

Corresponding proenzymes, where relevant, are shown in parentheses

Sucrase and a-dextrinase are separate subunits of a single protein

Table 26 5 Daily Water Turnover (mL) in the Gastrointestinal Tract.

Ingested Endogenous secretions Salivary glands Stomach Bile Pancreas Intestine Total input Reabsorbed Jejunum Ileum Colon 5500 2000 +1300 1500 2500 500 1500 +1000 =7000

2000 7000

9000 8800

=8800 Balance in stool 200

Table 26 7 Stimuli that Affect Gastrin Secretion.

Stimuli that increase gastrin secretion Luminal Peptides and amino acids Distention Neural Increased vagal discharge via GRP Bloodborne Calcium Epinephrine Stimuli that inhibit gastrin secretion Luminal Acid Somatostatin Bloodborne Secretin, GIP, VIP, glucagon, calcitonin

Table 27 1 Normal Transport of Substances by the Intestine and Location of Maximum Absorption or Secretion.a

Small Intestine Absorption of: Sugars (glucose, galactose, etc) Upperb Mid Lower Colon ++ +++ ++ 0

Amino acids Water-soluble and fat-soluble vitamins except vitamin B12 Betaine, dimethylglycine, sarcosine Antibodies in newborns Pyrimidines (thymine and uracil) Long-chain fatty acid absorption and conversion to triglyceride Bile acids Vitamin B12 Na K+ Ca2+ Fe2+ Cl SO42
+

++ +++ + + + +++ + 0 +++ + +++ +++ +++ ++

++ ++ ++ ++ + ++ + + ++ + ++ + ++ +

++ 0 ++ +++ ? + +++ +++ +++ + + + + 0

0 0 ? ? ? 0

0 +++ Sec ? ? + ?

Table 27 2 Factors Affecting the Metabolic Rate.

Muscular exertion during or just before measurement Recent ingestion of food High or low environmental temperature Height, weight, and surface area

Sex Age Growth Reproduction Lactation Emotional state Body temperature Circulating levels of thyroid hormones Circulating epinephrine and norepinephrine levels

Table 28 1 Mean Lengths of Various Segments of the Gastrointestinal Tract as Measured by Intubation in Living Humans.

Segment Pharynx, esophagus, and stomach Duodenum Jejunum and ileum Colon

Length (cm) 65 25 260 110

Table 29 1 Principal Functions of the Liver.

Formation and secretion of bile Nutrient and vitamin metabolism Glucose and other sugars Amino acids Lipids Fatty acids

Cholesterol Lipoproteins Fat-soluble vitamins Water-soluble vitamins Inactivation of various substances Toxins Steroids Other hormones Synthesis of plasma proteins Acute-phase proteins Albumin Clotting factors Steroid-binding and other hormone-binding proteins Immunity Kupffer cells

Table 30 1 Conduction Speeds in Cardiac Tissue.

Tissue SA node Atrial pathways AV node Bundle of His Purkinje system Ventricular muscle

Conduction Rate (m/s) 0.05 1 0.05 1 4 1

Table 30 2 ECG Intervals.

Normal Durations Intervals PR intervala QRS duration QT interval ST interval (QT minus QRS) Average Range 0.18b 0.08 0.40 0.32 Events in the Heart during Interval 0.12 0.20 Atrial depolarization and conduction through AV node to 0.10 to 0.43 ... Ventricular depolarization and atrial repolarization Ventricular depolarization plus ventricular repolarization Ventricular repolarization (during T wave)

Measured from the beginning of the P wave to the beginning of the QRS complex.

Shortens as heart rate increases from average of 0.18 s at a rate of 70 beats/min to 0.14 s at a rate of 130 beats/min.

Table 31 1 Variation in Length of Action Potential and Associated Phenomena with Cardiac Rate.a

Heart Rate 75/min Duration, each cardiac cycle Duration of systole Duration of action potential 0.80 0.27 0.25

Heart Rate 200/min 0.30 0.16 0.15 0.13 0.02 0.14

Skeletal Muscle ... ... 0.007 0.004 0.003 ...

Duration of absolute refractory 0.20 period Duration of relative refractory 0.05 period Duration of diastole 0.53

Table 31 3 Effect of Various Conditions on Cardiac Output.

Condition or Factora No change Sleep Moderate changes in environmental temperature Increase Anxiety and excitement (50 100%) Eating (30%) Exercise (up to 700%) High environmental temperature Pregnancy Epinephrine Decrease Sitting or standing from lying position (20 30%) Rapid arrhythmias Heart disease

Table 31 4 Changes in Cardial Function with Exercise. Note that Stroke Volume Levels off, Then Falls Somewhat (as a Result of the Shortening of Diastole) When the Heart Rate Rises to High Values.

Work (kg- O2 Usage m/min) (mL/min)

Pulse Cardiac Rate (per Output min) (L/min) 64 104 122 161 173 6.4 13.1 15.2 17.8 20.9

Stroke Volume (mL) 100 126 125 110 120

A-V O2 Difference (mL/dL) 4.3 7.0 9.4 12.3 14.5

Rest 288 540 900 1260

267 910 1430 2143 3007

Table 32 1 Normal Values for the Cellular Elements in Human Blood.

Cell Cells/ L (average) Total white blood 9000 cells Granulocytes Neutrophils Eosinophils Basophils Lymphocytes Monocytes Erythrocytes Females Males Platelets 4.8 x 106 5.4 x 106 300,000 5400 275 35 2750 540

Approximate Normal Range 4000 11,000

Percentage of Total White Cells ...

3000 6000 150 300 0 100 1500 4000 300 600 ... ... 200,000 500,000

50 70 1 4 0.4 20 40 2 8 ... ... ...

Table 33 1 Summary of Factors Affecting the Caliber of the Arterioles.

Constriction Local factors

Dilation

Decreased local temperature Autoregulation

Increased CO2 and decreased O2 Increased K+, adenosine, lactate, etc Decreased local pH Increased local temperature

Endothelial products Endothelin-1 Thromboxane A2 Circulating hormones Epinephrine (except in skeletal muscle and liver) Norepinephrine AVP Angiotensin II Circulating Na -K ATPase inhibitor Neuropeptide Y Neural factors Increased discharge of sympathetic Decreased discharge of sympathetic nerves nerves Activation of sympathetic cholinergic vasodilator nerves to skeletal muscle
+ +

NO Prostacyclin

Locally released platelet serotonin Kinins

Epinephrine in skeletal muscle and liver CGRP alpha Substance P Histamine ANP

VIP

The terms vasoconstriction and vasodilation are generally used to refer to constriction and dilation of the resistance vessels. Changes in the caliber of the veins are referred to specifically as venoconstriction or venodilation.

Table 34 1 Resting Blood Flow and O2 Consumption of Various Organs in a 63-kg Adult Man with a Mean Arterial Blood Pressure of 90 mm Hg and an O2 Consumption of 250 mL/min.

Arteriove nous Oxygen Regi Ma mL/m mL/1 Difference (mL/L) on ss in 00 (kg g/mi ) n Liver 2.6 1500 Kidn 0.3 1260 eys Brain 1.4 750 Skin 3.6 462 57.7 34 420.0 14 54.0 12.8 2.7 62 25 60

Blood Flow

Oxygen Resistance Percentage of Consumptio (R units)a Total n mL/m mL/1 Absol per Cardi Oxygen in 00 ute kg ac Consump g/mi Outp tion n ut 51 18 46 12 50 2.0 6.0 3.3 0.3 0.2 3.6 4.3 7.2 11.7 6.4 9.4 27.8 1.3 23.3 10. 13.9 1 42. 8.6 1 198 15.6 .4 20.4 7.2 18.4 4.8 20.0

Skele 31. 840 tal 0 muscl e Heart 0.3 250 muscl e Rest 23. 336 of 8 body Whol 63. 5400 e 0 body

84.0

114

29

9.7

21.4

6.4 4.7

11.6

1.4

129

44

0.2

16.1

383 6.2 .2

17.6

8.6

46

250

0.4

1.0

63. 100.0 100.0 0

Table 34 2 Concentration of Various Substances in Human CSF and Plasma.

Substance Na K+ Mg2+ Ca2+

+

CSF (meq/kg H2O) (meq/kg H2O) (meq/kg H2O) (meq/kg H2O)

Plasma

Ratio CSF/Plasma 0.98 0.62 1.39 0.49

147.0 150.0 2.9 2.2 2.3 4.6 1.6 4.7

Cl HCO3 PCO2 pH Osmolality Protein Glucose Inorganic P Urea Creatinine Uric acid Cholesterol

(meq/kg H2O) (meq/L) (mm Hg)

113.0 99.0 25.1 50.2 7.33 24.8 39.5 7.40

1.14 1.01 1.28 ... 1.00 0.003 0.64 0.73 0.80 1.25 0.30 0.001

(mosm/kg H2O) (mg/dL) (mg/dL) (mg/dL) (mg/dL) (mg/dL) (mg/dL) (mg/dL)

289.0 289.0 20.0 64.0 3.4 12.0 1.5 1.5 0.2 6000.0 100.0 4.7 15.0 1.2 5.0 175.0

Table 34 4 Pressure in Aorta and Left and Right Ventricles (Vent) in Systole and Diastole.

Pressure (mm Hg) in Aorta Left Vent Systole 120 Diastole 80 121 0 Right Vent 25 0

Pressure Differential (mm Hg) between Aorta and Left Vent 1 80 Right Vent 95 80

Table 36 3 Plasma pH, HCO3 , and PCO2 Values in Various Typical Disturbances of Acid-Base Balance.a

Arterial Plasma

Condition

pH HCO3 (mEq/L) 7.40 24.1 7.28 18.1 6.96 5.0

PCO2 (mm Cause Hg) 40 40 23 40 58 48 64 27 26 NH4 Cl ingestion Diabetic acidosis NaHCO3 ingestion Prolonged vomiting Breathing 7% CO2 Emphysema Voluntary hyperventilation Three-week residence at 4000m altitude

Normal Metabolic acidosis Metabolic alkalosis Respiratory acidosis Respiratory alkalosis

7.50 30.1 7.56 49.8 7.34 25.0 7.34 33.5 7.53 22.0 7.48 18.7

In the diabetic acidosis and prolonged vomiting examples, respiratory compensation for primary metabolic acidosis and alkalosis has occurred, and the Pco2 has shifted from 40 mm Hg. In the emphysema and high-altitude examples, renal compensation for primary respiratory acidosis and alkalosis has occurred and has made the deviations from normal of the plasma HCO3 larger than they would otherwise be.

Table 38 3 Agents Causing Contraction or Relaxation of Mesangial Cells.

Contraction Endothelins Angiotensin II Vasopressin Norepinephrine Platelet-activating factor Platelet-derived growth factor

Relaxation ANP Dopamine PGE2 cAMP

Thromboxane A2 PGF2 Leukotrienes C4 and D4 Histamine

Table 38 6 Transport Proteins Involved in the Movement of Na+ and Cl Across the Apical Membranes of Renal Tubular Cells.a

Site Proximal tubule

Apical Transporter Function Na/glucose CT Na+/Pi CT Na+ amino acid CT Na/lactate CT Na/H exchanger Cl/base exchanger Na+ uptake, glucose uptake Na+ uptake, Pi uptake Na+ uptake, amino acid uptake Na+ uptake, lactate uptake Na+ uptake, H+ extrusion Cl uptake Na+ uptake, Cl uptake, K+ uptake Na+ uptake, H+ extrusion K+ extrusion (recycling) Na+ uptake, Cl uptake

Thick ascending limb

Na K 2Cl CT Na/H exchanger K+ channels

Distal convoluted tubule NaCl CT Collecting duct

Na+ channel (ENaC) Na+ uptake

Uptake indicates movement from tubular lumen to cell interior, extrusion is movement from cell interior to tubular lumen. CT, cotransporter; Pi, inorganic phosphate.

Table 38 8 Permeability and Transport in Various Segments of the Nephron.a

Permeability H2O Urea NaCl Active Transport of Na+ Loop of Henle Thin descending limb Thin ascending limb Thick ascending limb Distal convoluted tubule Collecting tubule Cortical portion Outer medullary portion Inner medullary portion 3+* 0 3+* 0 3+* 3+ 2+ 1+ 1+ 4+ 0 0 + + 4+ 0 0 4+ 3+

Table 38 10 Mechanism of Action of Various Diuretics.

Agent Water Ethanol Antagonists of V2 vasopressin receptors such as astolvaptan

Mechanism of Action Inhibits vasopressin secretion. Inhibits vasopressin secretion. Inhibit action of vasopressin on collecting duct.

Large quantities of osmotically active Produce osmotic diuresis. substances such as mannitol and glucose Xanthines such as caffeine and theophylline Acidifying salts such as CaCl2 and NH4Cl Decrease tubular reabsorption of Na+ and increase GFR. Supply acid load; H+ is buffered, but an anion is excreted with Na+ when the ability of the kidneys to replace Na+ with H+ is exceeded. Decrease H+ secretion, with resultant increase in Na+ and K+ excretion. Inhibit the Na Cl cotransporter in the early portion of the distal tubule. Inhibit the Na K 2Cl cotransporter in the medullary thick ascending limb of the loop of Henle Inhibit Na+ K+ "exchange" in the collecting ducts by inhibiting the action of aldosterone (spironolactone) or by inhibiting the ENaCs (amiloride).

Carbonic anhydrase inhibitors such as acetazolamide (Diamox) Metolazone (Zaroxolyn), thiazides such as chlorothiazide (Diuril) Loop diuretics such as furosemide (Lasix), ethacrynic acid (Edecrin), and bumetanide K+-retaining natriuretics such as spironolactone (Aldactone), triamterene (Dyrenium), and amiloride (Midamor)

Table 39 1 Summary of Stimuli Affecting Vasopresson Secretion.

Vasopressin Secretion Increased Increased effective osmotic pressure of plasma Decreased ECF volume Pain, emotion, "stress," exercise Nausea and vomiting Standing

Vasopressin Secretion Decreased Decreased effective osmotic pressure of plasma Increased ECF volume Alcohol

Clofibrate, carbamazepine Angiotensin II

Table 39 2 Factors that Affect Renin Secretion.

Stimulatory Increased sympathetic activity via renal nerves Increased circulating catecholamines Prostaglandins Inhibitory Increased Na+ and Cl reabsorption across macula densa Increased afferent arteriolar pressure Angiotensin II Vasopressin

Table 39 3 Conditions that Increase Renin Secretion.

Na+ depletion Diuretics Hypotension Hemorrhage Upright posture Dehydration Cardiac failure Cirrhosis Constriction of renal artery or aorta Various psychologic stimuli

Table 40 2 Principal Buffers in Body Fluids.

Blood

H2CO3 H+ + HCO3 HProt H+ + Prot HHb H+ + Hb

Interstitial fluid

H2CO3 H+ + HCO3

Intracellular fluid HProt H+ + Prot H2PO4 H+ + HPO42

Table 58 4 Comparison of Th-1 Cells and Th-2 Cells

Property Produces IL-2 and gamma interferon Produces IL-4, IL-5, IL-6, and IL-10

Th-1 Cells Yes No

Th-2 Cells No Yes No Yes No Yes

Enhances cell-mediated immunity and delayed hypersensitivity Yes primarily Enhances antibody production primarily Stimulated by IL-12 Stimulated by IL-4 Table 58 7 Important Functions of the Main Cytokines No Yes No

Major Source

Cytokine

Important Functions

Macrophages

Interleukin-1 Interleukin-6

Proinflammatory cytokine. Induces fever. Induces liver to produce acute phase proteins. Proinflammatory cytokine. Induces fever. Induces liver to produce acute phase proteins.

Tumor necrosis Proinflammatory cytokine. Low concentration: factor activates neutrophils and increases their adhesion to endothelial cells. High concentration: mediates septic shock, acts as cachectin, causes necrosis of tumors. Interleukin-12 Th-1 subset of helper T cells Interleukin-2 Drives development of Th-1 subset of T cells. T-cell growth factor. Stimulates growth of both helper (CD4) and cytotoxic (CD8) T cells. Stimulates phagocytosis and killing by macrophages. Increases class I and II MHC protein expression. Inhibits growth of Th-2 cells. Drives development of Th-2 subset of T cells. Stimulates B-cell growth. Increases isotype class switching to IgE. Increases number of eosinophils. Increases isotype class switching to IgA. Antiinflammatory cytokine. Inhibits development of Th1 subset of T cells. Recruits neutrophils to site of infection. Important in gut mucosal immunity. Antiinflammatory cytokine. Inhibits activation of T cells. Increases isotype switching to IgA.

Gamma interferon

Th-2 subset of helper T cells

Interleukin-4

Interleukin-5 Interleukin-10 Th-17 subset of T cells Many cells including macrophages, T cells, and B cells. Interleukin-17 Transforming Growth Factorbeta

Table 59 1 Properties of Human Immunoglobulins

Property Percentage of total

lgG 75

lgA 15

lgM 9

lgD 0.2

lgE 0.004

immunoglobulin in serum (approx) Serum concentration (mg/dL) (approx) 1000 200 7S or 11S1 120 19S 3 7S 180 0.05 8S 190

Sedimentation coefficient 7S Molecular weight (x1000) 150 Structure H chain symbol Complement fixation Transplacental passage Mediation of allergic responses Found in secretions Opsonization Antigen receptor on B cell Polymeric form contains J chain + + +

170 or 4001 900

Monomer Monomer or dimer

Monomer or Monomer Monomer pentamer E

+ +

+ + +
2

Table 62 1 Comparison of Class I and Class II MHC Proteins

Feature Present antigen to CD4-positive cells Present antigen to CD8-positive cells Found on surface of all nucleated cells Found on surface of "professional" antigenpresenting cells, such as dendritic cells, macrophages, and B cells Encoded by genes in the HLA locus Expression of genes is codominant Multiple alleles at each gene locus

Class I MHC Class II MHC Proteins Proteins No Yes Yes Yes

1

Yes No No Yes

Yes Yes Yes

Yes Yes Yes Yes

Composed of two peptides encoded in the HLA locus No

Composed of one peptide encoded in the HLA locus and a -beta2-microglobulin Table 64 2 ABO Blood Groups

Yes

No

Group Antigen on Red Cell Antibody in Plasma A B AB O A B A and B No A or B Anti-B Anti-A No anti-A or anti-B Anti-A and anti-B

Table 64 3 Compatibility of Blood Transfusions between ABO Blood Groups1

Recipient Donor O A (AA or AO) B (BB or BO) AB O Yes No No No A Yes Yes No No B Yes No Yes No AB Yes Yes Yes Yes

Table 64 4 Rh Status and Hemolytic Disease of the Newborn

Rh Status Father Mother Child Hemolysis1 + + + + + or No + No (1st child) Yes (2nd child and subsequent children) No

+ or No No

Table 66 2 Microbial Infections Associated with Autoimmune Diseases

Microbe 1. Bacteria Streptococcus pyogenes Campylobacter jejuni Escherichia coli Chlamydia trachomatis Shigella species Yersinia enterocolitica Borrelia burgdorferi 2. Viruses Hepatitis B virus1 Hepatitis C virus Measles virus Coxsackie virus B3 Coxsackie virus B4 Cytomegalovirus Human T-cell leukemia virus
2 3

Autoimmune Disease Rheumatic fever Guillain-Barr syndrome Primary biliary cirrhosis Reiter's syndrome Reiter's syndrome Reactive arthritis Lyme arthritis Multiple sclerosis Mixed cryoglobulinemia Allergic encephalitis Myocarditis Type 1 diabetes mellitus Scleroderma HTLV-associated myelopathy

Cytokine IL-1 (, )

Table 7-1. Cytokines and Their Actions Major Cell Source Major Immunologic Action Macrophages Stimulates IL-2 receptor emergence in T Endothelial cells cells Dendritic cells Enhances B-cell activation Langerhans' cells Induces fever, acute phase reactants, and IL-6

IL-2 IL-3 IL-4 IL-5

TH1 cells T cells T cells T cells

IL-6

IL-7 IL-8

IL-9 IL-10 IL-11 IL-12

Monocytes T cells Endothelial cells Bone marrow Monocytes Endothelial cells Lymphocytes Fibroblasts TH cells TH2 cells Bone marrow Macrophages B cells

Increases nonspecific resistance Inhibited by an endogenous IL-1 receptor antagonist T-cell growth factor Activates NK and B cells Stimulates hematopoiesis Stimulates B-cell synthesis of IgE Down-regulation of IFN- Stimulates growth and differentiation of eosinophils B-cell growth factor Enhances IgA synthesis Induces acute phase reactants, fever, and late B-cell differentiation Stimulates pre B and pre T cells Chemotactic factor for neutrophils and T cells

IL-13 IL-15 IL-16

TH2 cells T cells CD8+ T cells Eosinophils T cells Activated macrophages Macrophages T cells B cells Large granular lymphocytes T cells

IL-17 IL-18 TNF-

T-cell mitogen Inhibits IFN- synthesis by TH1 cells Suppresses other cytokine synthesis Stimulates hematopoiesis Enhances acute phase protein synthesis Promotes TH1 differentiation and IFN- synthesis Stimulates NK cells and CD8+ T cells to cytolysis Acts synergistically with IL-2 Inhibits inflammatory cytokines (IL-1, IL-6, IL-8, IL-10, MCP) T-cell mitogen Enhances growth of intestinal epithelium Increases class II MHC, chemotaxis, and CD4+ T-cell cytokines Decreases antigen-induced proliferation Increases the inflammatory response Increases IFN- production and NK cell action Cytotoxic for tumors Causes cachexia Mediates bacterial shock

TNF-

Cytotoxic for tumors

Transforming growth Almost all normal cell Inhibits proliferation of both T and B factor types cells Reduces cytokine receptors Potent chemotactic agent for leukocytes Mediates inflammation and tissue repair IFN = interferon; Ig = immunoglobulin; IL = interleukin; MCP = macrophage chemotactic protein; MHC = major histocompatibility complex; NK = natural killer; TNF = tumor necrosis factor.

Acid/base compensation
The mnemonic ROME means the following: Respiratory Opposite
pH elevated PCO2 diminished = respiratory alkalosis pH diminished PCO2 elevated = respiratory acidosis

Metabolic Equal
pH elevated HCO3 elevated = metabolic alkalosis pH diminished HCO3 diminished = metabolic acidosis

Normal Values and Acceptable Ranges of the ABG Elements

pH 7.4 Range Range7.35to7.45 Pa02 80 to 90mm 100 40mm Hg mm 93 to Hg Hg 100% Sa02 PaC0 Range Range 2 Ran 24mE 35 to q/L 45 22 to mm 26mE Hg q/L Range HC0 3

7.35 to 7.45 Pa02

ge

Number One! Determine if the client is demonstrating an acidotic (remember: pH less than 7.35) or alkalotic (pH greater than 7.45). Number Two! What is the 'primary problem' If the client is acidotic with a PaC02 greater than 45 mmHg it is RESPIRATORY If the client is acidotic with a HC03 less than 22 mEq/L it is METABOLIC! If the client is alkalotic with a PaC02 less than 35 mmHg it is RESPIRATORY! If the client is alkalotic with a HC03 greater than 26 mEq/L it is METABOLIC! Number Three! Is the client compensating? Are both components (HCO3 and PaCO2) shifting in the same direction? Up or down the continuum? Above or below the normal ranges? If this is noted, you know that the client s buffering systems are functioning and are trying to bring the acid-base balance back to normal. Uncompensated pH abnormal (high or low)

One component abnormal (high or low CO2 or HCO3) The other component is normal (The component not causing the acidbase imbalance is still normal Partly compensated pH not normal (but moving toward normal) Both CO2 and HCO3 are outside normal range The component that was normal is changing in order to compensate Compensated pH normal Other values abnormal in opposite directions One is acidotic the other alkaline

Case Studies :: Case Study 1 A client recovering from surgery in the post-anesthesia care unit (PACU) is difficult to arouse two hours following surgery. The nurse in the PACU has been administering Morphine Sulfate intravenously to the client for complaints of post-surgical pain. The client s respiratory rate is 7 per minute and demonstrates shallow breathing. The patient does not respond to any stimuli!

The nurse assesses the ABCs (remember Airway, Breathing, Circulation!) and obtains ABGs STAT! The STAT results come back from the laboratory and show: pH = 7.15 Pa C02 = 68 mmHg HC03 = 22 mEq/L

Once you have interpreted the ABG results, click on one of the following
o

Compensated Respiratory Acidosis Uncompensated Metabolic Acidosis Compensated Metabolic Alkalosis Uncompensated Respiratory Acidosis ans

Case Studies :: Case Study 2 An infant, three weeks old, is admitted to the Emergency Room. The mother reports that the infant has been irritable, difficult to breastfeed and has had diarrhea for the past 4 days. The infant s respiratory rate is elevated and the fontanels are sunken. The Emergency Room physician orders ABGs after assessing the ABCs. The results from the ABGs come back from

the laboratory and show: pH = 7.37 Pa C02 = 29 mmHg HC03 = 17 mEq/L

Once you have interpreted the ABG results, click on one of the following

Compensated Respiratory Alkalosis Uncompensated Metabolic Acidosis Compensated Metabolic Acidosis ans Uncompensated Respiratory Acidosis

Case Studies :: Case Study 3 A client, 5 days post-abdominal surgery, has a nasogastric tube. The nurse notes that the nasogastric tube (NGT) is draining a large amount (900 cc in 2hours) of coffee ground secretions. The client is not oriented to person, place, or time. The nurse contacts the attending physician and STAT ABGs are ordered. The results from the ABGs come back from the laboratory and show: pH = 7.52 Pa C02 = 35 mmHg

HC03 = 29 mEq/L

Once you have interpreted the ABG results, click on one of the following Compensated Respiratory Alkalosis Uncompensated Metabolic Acidosis Compensated Metabolic Acidosis Uncompensated Metabolic Alkalosis ans Case Studies :: Case Study 4 A client is admitted to the hospital and is being prepared for a craniotomy (brain surgery). The client is very anxious and scared of the impending surgery. He begins to hyperventilate and becomes very dizzy. The client looses consciousness and the STAT ABGs reveal: The results from the ABGs come back from the laboratory and show: pH = 7.57 Pa C02 = 26 mmHg HC03 = 24 mEq/L

Once you have interpreted the ABG results, click on one of the following Compensated Metabolic Acidosis Uncompensated Metabolic Acidosis Uncompensated Respiratory Alkalosis Uncompensated Respiratory Acidosis Case Studies :: Case Study 5

ans

A two-year-old is admitted to the hospital with a diagnosis of asthma and respiratory distress syndrome. The father of the infant reports to the nurse that he has observed slight tremors and behavioral changes in his child over the past three days. The attending physician orders routine ABGs following an assessment of the ABCs. The ABG results are: The results from the ABGs come back from the laboratory and show: pH = 7.36 Pa C02 = 69 mmHg HC03 = 36 mEq/L

Once you have interpreted the ABG results, click on one of the following Compensated Respiratory Alkalosis Uncompensated Metabolic Acidosis

Compensated Respiratory Acidosis ans Uncompensated Respiratory Alkalosis